Abstract
Objective To investigate the molecular mechanisms of HCZP treatment of asthma. Materials and Methods Thirty Sprague Dawley (SD) rats were divided into normal, asthma, and HCZP groups (n = 10). The asthma model was sensitized by 1 mg ovalbumin (OVA)/aluminum hydroxide Al(OH)3mixture and then challenged with 1% aerosolized OVA for four weeks. Rats in the HCZP group received 10.08 g/kg/d HCZP for four weeks during OVA challenge. Then, lung tissues of rats in each group were collected for RNA sequencing. Moreover, the expression level of some core genes was detected by using western blotting and immunohistochemistry. Results Inflammatory cell infiltration and pathological damage of the lungs improved in the HCZP group. Compared with the asthma group (0.049 ± 0.002 mm2/mm; 0.036 ± 0.006 mm2/mm; and 0.014 ± 0.001 mm2/mm), total wall thickness (0.042 ± 0.001 mm2/mm), inner wall thickness (0.013 ± 0.001 mm2/mm), and smooth muscle layer thickness (0.012 ± 0.001 mm2/mm) significantly decreased in the HCZP group. Bioinformatics analysis showed that hub genes such as bradykinin receptor B2 (Bdkrb2) and CD4 molecule (Cd4) had different expression patterns between model and HCZP groups. Two transcription factors, forkhead box Q1 (Foxq1) and nuclear factor of activated T cells 2 (Nfatc2), served important regulatory roles in asthma. Compared with the model group, Bdkrb2 protein expression increased and Nfatc2 protein expression decreased in the HCZP group. Discussion and Conclusion. HCZP could alleviate asthma via regulating the expression of several hub genes, which might serve as therapeutic targets for asthma. However, the mechanism of these genes will be studied in the future.
Highlights
Asthma, a common chronic respiratory disease in children and adults, is characterized by reversible airway inflammation obstruction and bronchial hyperresponsiveness [1]
All animal protocols were approved by the Ethics Committee and Animal Management Committee of Wuhan Hospital of Traditional Chinese Medicine (Approved on 2017-06-02), which conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health [19]
Protein-Protein Interaction (PPI) analysis showed that CD4 molecule (Cd4) and bradykinin receptor B2 (Bdkrb2) were with higher degrees and might be considered as hub genes
Summary
A common chronic respiratory disease in children and adults, is characterized by reversible airway inflammation obstruction and bronchial hyperresponsiveness [1]. Pharmacotherapy of asthma mainly includes bronchodilators and anti-inflammatory drugs, such as β2-. Agonists and glucocorticoids [5]. Previous evidence indicates that β2-agonists are associated with an increased risk of myocardial infarction, congestive heart failure, and sudden cardiac death [6]; glucocorticoids possess extensive immunosuppressive activity and potentially serious side effects and may further promote human metapneumovirus infection which is capable of eliciting inflammatory responses [7]. Us, it is necessary to explore safe and effective drugs for asthma treatment. Traditional Chinese medicine (TCM), widely reported to be a complementary and alternative therapy for asthma attacks, can alleviate airway hypersensitivity and inflammatory cell infiltration in patients with asthma [8, 9] Previous evidence indicates that β2-agonists are associated with an increased risk of myocardial infarction, congestive heart failure, and sudden cardiac death [6]; glucocorticoids possess extensive immunosuppressive activity and potentially serious side effects and may further promote human metapneumovirus infection which is capable of eliciting inflammatory responses [7]. us, it is necessary to explore safe and effective drugs for asthma treatment.
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